YWHAG as a novel biomarker in Alzheimer's disease biological research framework

BackgroundYWHAG has been recognized as a promising biomarker for Alzheimer's disease (AD). However, the precise role of YWHAG within the revised 2024 diagnostic framework for AD remains unclear.ObjectiveOur study aimed to evaluate YWHAG with established biomarkers to delinea te the role of YWHAG and determine whether it could serve as a complementary biomarker within the 2024 diagnostic criteria.MethodsWe compared YWHAG with established biomarkers among 708 participants from Alzheimer's Disease Neuroimaging Initiative (ADNI) across three domains: 1) diagnostic utility, 2) cross-sectional associations with clinical variables and brain structure, and 3) predictive value for clinical progression risk.ResultsOur results demonstrated the accuracy of YWHAG (AUC = 0.856) was comparable to that of FDG-PET (AUC = 0.912) and HVA (AUC = 0.879), but superior to that of T-tau (AUC = 0.796), NFL (AUC = 0.712), and GFAP (AUC = 0.617) in distinguishing AD versus controls. Moreover, YWHAG was consistently among the top three biomarkers most strongly associated with cognitive decline and brain atrophy, alongside HVA and FDG-PET. Furthermore, the YWHAG positive (Y+) group had a significantly higher risk of AD progression (HR = 2.45, 95% CI: 1.75-3.43) compared to the YWHAG negative (Y-) group (p < 0.001).ConclusionsWe identify YWHAG as a novel biomarker predictive of cognitive decline, brain atrophy, and AD progression. The performances of YWHAG are comparable to established biomarkers such as FDG-PET, HVA and T-tau, thereby providing a complement to the current AD diagnostic framework.